Lyn-mediated down-regulation of B cell antigen receptor signaling: inhibition of protein kinase C activation by Lyn in a kinase-independent fashion.
Stimulation of the B cell Ag receptor (BCR) induces activation of tyrosine kinases such as Lyn and Syk, phosphorylation and activation of multiple signaling components, and eventually, the expression of several genes including c-myc. Syk is required for activation of phospholipase C-gamma 2 and the subsequent phosphatidylinositol hydrolysis, leading to protein kinase C (PKC) activation and intracellular Ca2+ increase. In contrast, the function of Lyn remains obscure. Here, we report that BCR-mediated induction of c-myc promoter activity and of PKC activity, but not the expression level of functional PKC, was markedly augmented in Lyn-deficient chicken B cells. This enhancement was reversed to the level of wild-type cells by the expression of exogenous Lyn of kinase-inactive form. These results indicate that Lyn inhibits BCR-mediated activation of a large portion of PKC isozymes in a kinase-independent fashion. This finding reveals a novel role of Lyn in negative regulation of BCR signaling.
Katsuta
H
H
Division of Molecular Biology, Research Institute for Biological Sciences, Science University of Tokyo, Chiba, Japan.
Tsuji
S
S
Niho
Y
Y
Kurosaki
T
T
Kitamura
D
D
D000818:Animals; D002645:Chickens; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology*; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology; D016259:Genes, myc / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D011401:Promoter Regions, Genetic / Q000276:immunology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019061:src-Family Kinases / Q000502:physiology*
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate